title: Genome-wide high density single-nucleotide polymorphism array-based karyotyping improves detection of clonal aberrations including der(9) deletion, but does not predict treatment outcomes after imatinib therapy in chronic myeloid leukemia.
abstract: The current study investigated molecular cytogenetic characteristics of chronic myeloid leukemia (CML) using genome-wide, single nucleotide polymorphism arrays (SNP-A) capable of detecting cryptic submicroscopic genomic aberrations. Genome-Wide Human SNP 6.0 Array (Affymetrix, CA, USA) was performed in 118 patients having CML, chronic phase. Thirty-nine clonal aberrations (CAs) were identified (35 losses, two gains, two copy neutral loss of heterozygosity) that were not detected by metaphase cytogenetics in 25 patients (21%). The 9q34 deletions were found in 10% of cases, while 22q11.2 deletions were observed in 12% of cases. Seven patients (6%) harbored both 5'-ABL and 3'-BCR deletions adjacent to the t(9;22) breakpoint. Copy number gains were identified at 8p and 9p, and losses at 2q, 7q, 8q, 9q, 11q, 13q, 16p, and 22q. When we compared the treatment outcome of imatinib therapy between patients with and without CAs identified by SNP-A, treatment failure and progression to advanced disease were not significantly different (p > 0.05). In addition, according to the presence of deletions of 9q34 and/or 22q11.2 identified by SNP-A, the treatment outcome did not show any significant differences (p > 0.05). Our data suggests that SNP-A analysis is a useful tool for detection of clonal aberrations including deletions adjacent to the t(9;22) breakpoint in the CML cancer genome. However, clonal aberrations detected by SNP-A could not improve a prognostic stratification in CML patients with chronic phase.
authors.affiliation: Department of Laboratory Medicine, Ewha Womans University School of Medicine, Seoul, South Korea.
authors.forename: Jungwon
authors.initials: J
authors.lastname: Huh
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Myung Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Yeo Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Hyeoung Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jang Soo
authors.initials: JS
authors.lastname: Suh
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.forename: Sang Kyung
authors.initials: SK
authors.lastname: Sohn
authors.forename: Goong Hyun
authors.initials: GH
authors.lastname: Nam
authors.forename: Jong-eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Dong Hwan Dennis
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping / Q000379:methods*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate